Robert Silverman

Summary

Affiliation: Cleveland Clinic Foundation
Country: USA

Publications

  1. pmc Selection and cloning of poly(rC)-binding protein 2 and Raf kinase inhibitor protein RNA activators of 2',5'-oligoadenylate synthetase from prostate cancer cells
    Ross J Molinaro
    Department of Chemistry, Cleveland State University, Euclid Avenue at East 24th Street, Cleveland, OH 44115, USA
    Nucleic Acids Res 34:6684-95. 2006
  2. pmc RNase L restricts the mobility of engineered retrotransposons in cultured human cells
    Ao Zhang
    Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland Clinic, Cleveland, OH, 44195, USA, Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA, Department of Human Genetics, Ann Arbor, MI 48109, USA, Cellular and Molecular Biology Program, Ann Arbor, MI 48109, USA, Department of Internal Medicine, Ann Arbor, MI 48109, USA and Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA
    Nucleic Acids Res 42:3803-20. 2014
  3. pmc XMRV Discovery and Prostate Cancer-Related Research
    David E Kang
    Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Adv Virol 2011:432837. 2011
  4. pmc Absence of XMRV and closely related viruses in primary prostate cancer tissues used to derive the XMRV-infected cell line 22Rv1
    Jaydip Das Gupta
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America
    PLoS ONE 7:e36072. 2012
  5. pmc Characterization of antibodies elicited by XMRV infection and development of immunoassays useful for epidemiologic studies
    Xiaoxing Qiu
    Infectious Diseases R and D, Abbott Diagnostics, 100 Abbott Park Rd, Abbott Park, IL 60064, USA
    Retrovirology 7:68. 2010
  6. pmc The xenotropic murine leukemia virus-related retrovirus debate continues at first international workshop
    Jonathan P Stoye
    MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW71AA, UK
    Retrovirology 7:113. 2010
  7. pmc A scientific journey through the 2-5A/RNase L system
    Robert H Silverman
    Department of Cancer Biology, NB40 Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Cytokine Growth Factor Rev 18:381-8. 2007
  8. doi request reprint The human retrovirus XMRV in prostate cancer and chronic fatigue syndrome
    Robert H Silverman
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Nat Rev Urol 7:392-402. 2010
  9. ncbi request reprint Implications for RNase L in prostate cancer biology
    Robert H Silverman
    Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Biochemistry 42:1805-12. 2003
  10. ncbi request reprint Suppression of ovarian carcinoma cell growth in vivo by the interferon-inducible plasma membrane protein, phospholipid scramblase 1
    Robert H Silverman
    Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Cancer Res 62:397-402. 2002

Research Grants

  1. Antiviral Mechanisms of 2-5A Dependent RNase L
    Robert H Silverman; Fiscal Year: 2010
  2. Antiviral Mechanisms of 2-5A Dependent RNase L
    Robert Silverman; Fiscal Year: 2007
  3. Role of RNase L in the Biology of Prostate Cancer
    Robert Silverman; Fiscal Year: 2006
  4. Antiviral Mechanisms of 2 5A Dependent RNase L
    Robert Silverman; Fiscal Year: 2004
  5. Antiviral Mechanisms of 2 5A Dependent RNase L
    Robert Silverman; Fiscal Year: 2003
  6. Role of Phospholipid Scramblase in Interferon Action
    Robert Silverman; Fiscal Year: 2002
  7. REGULATION OF 2-5A-DEPENDENT RNASE LEVELS OF INTERFERON
    Robert Silverman; Fiscal Year: 1993
  8. ANTIVIRAL MECHANISMS OF 2 5A DEPENDENT RNASE
    Robert Silverman; Fiscal Year: 1999
  9. REGULATION OF 2-5A-DEPENDENT RNASE LEVELS OF INTERFERON
    Robert Silverman; Fiscal Year: 1992
  10. Role of Phospholipid Scramblase in Interferon Action
    Robert Silverman; Fiscal Year: 2004

Collaborators

Detail Information

Publications73

  1. pmc Selection and cloning of poly(rC)-binding protein 2 and Raf kinase inhibitor protein RNA activators of 2',5'-oligoadenylate synthetase from prostate cancer cells
    Ross J Molinaro
    Department of Chemistry, Cleveland State University, Euclid Avenue at East 24th Street, Cleveland, OH 44115, USA
    Nucleic Acids Res 34:6684-95. 2006
    ..Results suggest that OAS activation may occur in prostate cancer cells in vivo stimulated by cellular mRNAs for RKIP and PCBP2...
  2. pmc RNase L restricts the mobility of engineered retrotransposons in cultured human cells
    Ao Zhang
    Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland Clinic, Cleveland, OH, 44195, USA, Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA, Department of Human Genetics, Ann Arbor, MI 48109, USA, Cellular and Molecular Biology Program, Ann Arbor, MI 48109, USA, Department of Internal Medicine, Ann Arbor, MI 48109, USA and Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA
    Nucleic Acids Res 42:3803-20. 2014
    ..Together, these data suggest that RNase L might function as a suppressor of structurally distinct retrotransposons. ..
  3. pmc XMRV Discovery and Prostate Cancer-Related Research
    David E Kang
    Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Adv Virol 2011:432837. 2011
    ..XMRV also traffics to prostate in a nonhuman primate model of infection. Here, we will review the discovery of XMRV and then focus on prostate cancer-related research involving this intriguing virus...
  4. pmc Absence of XMRV and closely related viruses in primary prostate cancer tissues used to derive the XMRV-infected cell line 22Rv1
    Jaydip Das Gupta
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America
    PLoS ONE 7:e36072. 2012
    ..Our findings confirm and reinforce the conclusion that XMRV is a recombinant laboratory-generated mouse virus that is highly adapted for human prostate cancer cells...
  5. pmc Characterization of antibodies elicited by XMRV infection and development of immunoassays useful for epidemiologic studies
    Xiaoxing Qiu
    Infectious Diseases R and D, Abbott Diagnostics, 100 Abbott Park Rd, Abbott Park, IL 60064, USA
    Retrovirology 7:68. 2010
    ..Development of assays to detect XMRV-specific antibodies would greatly facilitate such studies. However, the nature and kinetics of the antibody response to XMRV infection have yet to be determined...
  6. pmc The xenotropic murine leukemia virus-related retrovirus debate continues at first international workshop
    Jonathan P Stoye
    MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW71AA, UK
    Retrovirology 7:113. 2010
    ..The current status of XMRV research, concerns among the scientific community and suggestions for future actions are summarized in this meeting report...
  7. pmc A scientific journey through the 2-5A/RNase L system
    Robert H Silverman
    Department of Cancer Biology, NB40 Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Cytokine Growth Factor Rev 18:381-8. 2007
    ..My scientific journey through the 2-5A system recounts some of the highlights of these efforts. Knowledge gained from studies on the 2-5A system could have an impact on development of therapies for important viral pathogens and cancer...
  8. doi request reprint The human retrovirus XMRV in prostate cancer and chronic fatigue syndrome
    Robert H Silverman
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Nat Rev Urol 7:392-402. 2010
    ..Emerging science surrounding XMRV is contributing to our knowledge of retroviral infections while focusing intense interest on two major human diseases...
  9. ncbi request reprint Implications for RNase L in prostate cancer biology
    Robert H Silverman
    Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Biochemistry 42:1805-12. 2003
    ..This monograph reviews the biochemistry and genetics of RNase L as it relates to the pathobiology of prostate cancer and considers implications for future screening and therapy of this disease...
  10. ncbi request reprint Suppression of ovarian carcinoma cell growth in vivo by the interferon-inducible plasma membrane protein, phospholipid scramblase 1
    Robert H Silverman
    Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Cancer Res 62:397-402. 2002
    ..These data suggest that the up-regulation of PLSCR1 expression in tumor cells exposed to IFN may contribute to the observed tumor-suppressive action of this cytokine...
  11. pmc Viral encounters with 2',5'-oligoadenylate synthetase and RNase L during the interferon antiviral response
    Robert H Silverman
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue NB40, Cleveland, OH 44195, USA
    J Virol 81:12720-9. 2007
  12. ncbi request reprint Skin allograft rejection is suppressed in mice lacking the antiviral enzyme, 2',5'-oligoadenylate-dependent RNase L
    Robert H Silverman
    Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Ohio 44195, USA
    Viral Immunol 15:77-83. 2002
    ..Results consistent with a proinflammatory role for RNase L extend the known functions of the 2-5A/RNase L system beyond innate immunity into some, but not all, types of cellular immunity...
  13. pmc Phospholipid scramblase 1 potentiates the antiviral activity of interferon
    Beihua Dong
    Department of Cancer Biology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Virol 78:8983-93. 2004
    ..Our results suggest that PLSCR1, which is itself an ISG-encoded protein, provides a mechanism for amplifying and enhancing the IFN response through increased expression of a select subset of potent antiviral genes...
  14. doi request reprint Pathological aggressiveness of prostatic carcinomas related to RNASEL R462Q allelic variants
    Benjamin T Larson
    Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland Clinic, Cleveland, Ohio, USA
    J Urol 179:1344-8. 2008
    ..We assessed a series of men undergoing radical prostatectomy for clinical and pathological measures of tumor aggressiveness according to the RNASEL R462Q genotype...
  15. ncbi request reprint Tumour suppressor function of RNase L in a mouse model
    Wendy Liu
    Department of Chemistry, Clinical Chemistry Program, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115, USA
    Eur J Cancer 43:202-9. 2007
    ..Further analysis revealed, however, that these tumours no longer expressed ectopic RNase L. Our findings suggest that RNase L plays a critical role in the inhibition of fibrosarcoma growth in nude mice...
  16. ncbi request reprint RNASEL Arg462Gln variant is implicated in up to 13% of prostate cancer cases
    Graham Casey
    Department of Cancer Biology, ND50, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Nat Genet 32:581-3. 2002
    ..Men that are heterozygous with respect to the mutated allele have 50% greater risk of prostate cancer than non-carriers, and homozygotes have more than double the risk...
  17. ncbi request reprint An apoptotic signaling pathway in the interferon antiviral response mediated by RNase L and c-Jun NH2-terminal kinase
    Geqiang Li
    Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 279:1123-31. 2004
    ..These findings suggest that JNK and RNase L function in an integrated signaling pathway during the IFN response that leads to elimination of virus-infected cells through apoptosis...
  18. ncbi request reprint Interferons at age 50: past, current and future impact on biomedicine
    Ernest C Borden
    Taussig Cancer Center, Case Comprehensive Cancer Center, Mellen Center for Multiple Sclerosis, and Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Nat Rev Drug Discov 6:975-90. 2007
    ..Our goal is to offer a molecular and clinical perspective that will enable IFNs or their TLR agonist inducers to reach their full clinical potential...
  19. doi request reprint Inflammation, infection, and prostate cancer
    Eric A Klein
    Glickman Urologic and Kidney Institute, Cleveland, Ohio, USA
    Curr Opin Urol 18:315-9. 2008
    ..Recent evidence suggesting that inflammation and infection play a role in the etiology of prostate cancer, and the discovery of a novel virus in men with a genetic susceptibility to prostate cancer is reviewed...
  20. pmc A transcriptional signaling pathway in the IFN system mediated by 2'-5'-oligoadenylate activation of RNase L
    Krishnamurthy Malathi
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Proc Natl Acad Sci U S A 102:14533-8. 2005
    ..Because 2-5A and RNase L participate in defenses against viral infections and prostate cancer, our findings have implications for basic cellular mechanisms that control major pathogenic processes...
  21. ncbi request reprint Genetic susceptibility and oxidative stress in prostate cancer: integrated model with implications for prevention
    Eric A Klein
    Section of Urologic Oncology, Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44122, USA
    Urology 68:1145-51. 2006
  22. pmc An infectious retrovirus susceptible to an IFN antiviral pathway from human prostate tumors
    Beihua Dong
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Proc Natl Acad Sci U S A 104:1655-60. 2007
    ..Our studies demonstrate that XMRV is a virus that has infected humans and is susceptible to inhibition by IFN and its downstream effector, RNase L...
  23. ncbi request reprint 2-5A ligands--a new concept for the treatment of prostate cancer
    Hagen Cramer
    Ridgeway Biosystems Inc, Cleveland, Ohio, USA
    Nucleosides Nucleotides Nucleic Acids 26:1471-7. 2007
    ..78 nM) as a folate hydrolase inhibitor, while SMCC 2-5A lacking the ZJ-24 part, did not show much activity (IC50 = 1974 nM). Also, RBI 1033's affinity to PSMA was found to be 10 times higher than ZJ-24 itself...
  24. pmc Small-molecule activators of RNase L with broad-spectrum antiviral activity
    Chandar S Thakur
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Proc Natl Acad Sci U S A 104:9585-90. 2007
    ..Therefore, these RNase L activators are prototypes for a previously uncharacterized class of broad-spectrum antiviral agents...
  25. pmc RNase L mediated protection from virus induced demyelination
    Derek D C Ireland
    Department of Neuroscience, Lerner Research Institute, The Cleveland Clinic, Cleveland, Ohio, United States of America
    PLoS Pathog 5:e1000602. 2009
    ..Protective function is rather associated with cell type specific and regional restriction of viral replication in grey matter and ameliorated neurodegeneration and demyelination...
  26. pmc RNase L releases a small RNA from HCV RNA that refolds into a potent PAMP
    Krishnamurthy Malathi
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
    RNA 16:2108-19. 2010
    ..It is proposed that RNase L mediated cleavage of HCV RNA generates svRNA that activates RIG-I, thus propagating innate immune signaling to the IFN-β gene...
  27. ncbi request reprint Targeted therapy of respiratory syncytial virus in African green monkeys by intranasally administered 2-5A antisense
    Douglas W Leaman
    Ridgeway Biosystems Inc, 9500 Euclid Avenue, NE50, Cleveland, Ohio 44195, USA
    Virology 292:70-7. 2002
    ..When administered intranasally to RSV-infected African green monkeys, this chimera reduced nasal RSV replication by up to four log(10) units in a dose- and time-dependent manner...
  28. ncbi request reprint HPC1/RNASEL mediates apoptosis of prostate cancer cells treated with 2',5'-oligoadenylates, topoisomerase I inhibitors, and tumor necrosis factor-related apoptosis-inducing ligand
    Krishnamurthy Malathi
    Department of Cancer Biology, Lerner Research Institute, and Experimental Therapeutics Program, Taussig Cancer Center, The Cleveland Clinic Foundation, Cleveland, Ohio, USA
    Cancer Res 64:9144-51. 2004
    ..These findings indicate that RNase L integrates and amplifies apoptotic signals generated during treatment of prostate cancer cells with 2-5A, Topo I inhibitors, and TRAIL...
  29. pmc Blockade of interferon induction and action by the E3L double-stranded RNA binding proteins of vaccinia virus
    Ying Xiang
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
    J Virol 76:5251-9. 2002
    ..Furthermore, our results indicate the existence of an interferon-mediated antipoxvirus pathway that operates independently of PKR, Mx1, or the 2-5A/RNase L system...
  30. pmc Small self-RNA generated by RNase L amplifies antiviral innate immunity
    Krishnamurthy Malathi
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Nature 448:816-9. 2007
    ..Our results indicate that RNase L has an essential role in the innate antiviral immune response that relieves the requirement for direct sensing of non-self RNA...
  31. pmc Inhibition of human parainfluenza virus type 3 infection by novel small molecules
    Hongxia Mao
    Department of Molecular Genetics, Virology Section NN10, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Antiviral Res 77:83-94. 2008
    ..Use of these inhibitors has a strong potential to develop novel antiviral agents against this important human pathogen...
  32. pmc Fibrils of prostatic acid phosphatase fragments boost infections with XMRV (xenotropic murine leukemia virus-related virus), a human retrovirus associated with prostate cancer
    Seunghee Hong
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
    J Virol 83:6995-7003. 2009
    ....
  33. pmc Down-regulation of p53 by double-stranded RNA modulates the antiviral response
    Joao T Marques
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, OH 44195, USA
    J Virol 79:11105-14. 2005
    ..Hence, our data suggest that the down-regulation of p53 facilitates apoptosis, thereby limiting viral replication...
  34. ncbi request reprint Effects of RNase L mutations associated with prostate cancer on apoptosis induced by 2',5'-oligoadenylates
    Ying Xiang
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Cancer Res 63:6795-801. 2003
    ..Our findings support the notion that RNASEL mutations and some variants allow tumor cells to escape a potent apoptotic pathway...
  35. ncbi request reprint Human telomerase RNA degradation by 2'-5'-linked oligoadenylate antisense chimeras in a cell-free system, cultured tumor cells, and murine xenograft models
    Jayashree M Paranjape
    Department of Cancer Biology and Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
    Oligonucleotides 16:225-38. 2006
    ....
  36. pmc Protein kinase R-dependent regulation of interleukin-10 in response to double-stranded RNA
    Arindam Chakrabarti
    Departments of Cancer Biology and Molecular Cardiology, Lerner Research Institute, The Cleveland Clinic, Cleveland, OH 44195, USA
    J Biol Chem 283:25132-9. 2008
    ..Together, our data demonstrate the role of PKR in regulating an anti-inflammatory cytokine. The findings have significance in antiviral as well as broader innate immune responses...
  37. ncbi request reprint Activation of the interferon system by short-interfering RNAs
    Carol A Sledz
    Department of Cancer Biology, Lerner Research Institute, NB40, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195 USA
    Nat Cell Biol 5:834-9. 2003
    ..Thus, siRNAs have broad and complicating effects beyond the selective silencing of target genes when introduced into cells. This is of critical importance, as siRNAs are currently being explored for their potential therapeutic use...
  38. pmc Androgen stimulates transcription and replication of xenotropic murine leukemia virus-related virus
    Beihua Dong
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    J Virol 84:1648-51. 2010
    ..Findings suggest that integration of the XMRV long terminal repeat (LTR) into host DNA could impart androgen stimulation on cellular genes...
  39. ncbi request reprint Proteasome-mediated degradation of RNase L in response to phorbol-12-myristate-13-acetate (PMA) treatment of mouse L929 cells
    Barbara I Chase
    Department of Chemistry, Cleveland State University, Cleveland, OH 44115, USA
    J Interferon Cytokine Res 23:565-73. 2003
    ..These inhibitors completely blocked the degradation of RNase L caused by PMA. Our results show a novel regulatory pathway for RNase L that could have an impact on its antitumor and antiviral functions...
  40. ncbi request reprint Mapping of the human RNASEL promoter and expression in cancer and normal cells
    Aimin Zhou
    Department of Chemistry, Cleveland State University, Cleveland, OH 44115, USA
    J Interferon Cytokine Res 25:595-603. 2005
    ..Our findings are the first description of the human RNASEL promoter that allows constituitive expression in a range of normal and neoplastic cell types...
  41. pmc A natural human retrovirus efficiently complements vectors based on murine leukemia virus
    Beihua Dong
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America
    PLoS ONE 3:e3144. 2008
    ..The similarity between the MLV and XMRV genomes suggests a possibility that the two viruses may interact when present in the same cell...
  42. pmc Integration site preference of xenotropic murine leukemia virus-related virus, a new human retrovirus associated with prostate cancer
    Sanggu Kim
    Biomedical Engineering Interdepartmental Program, UCLA School of Medicine, Los Angeles, CA 90095, USA
    J Virol 82:9964-77. 2008
    ..These results are consistent with a model in which XMRV may contribute to tumorigenicity via a paracrine mechanism...
  43. pmc Diverse functions of RNase L and implications in pathology
    Catherine Bisbal
    IGH UPR CNRS 1142, 141 rue de la Cardonille, 34396 Montpellier, France
    Biochimie 89:789-98. 2007
    ..Several recent studies have suggested that RNase L could have a role in cancer biology and evidence of a tumor suppressor function of RNase L has emerged from studies on the genetics of hereditary prostate cancer...
  44. ncbi request reprint An alternative spliced RNASEL variant in peripheral blood leukocytes
    Hanna Rennert
    Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY 10012, USA
    J Interferon Cytokine Res 26:820-6. 2006
    ..Our results suggest that RNase L plays an important role in granulocytes as an innate immunity enzyme that controls viral infections...
  45. pmc Functional replacement of the carboxy-terminal two-thirds of the influenza A virus NS1 protein with short heterologous dimerization domains
    Xiuyan Wang
    Department of Microbiology, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA
    J Virol 76:12951-62. 2002
    ..These results suggest that the main biological function of the carboxy-terminal region of the NS1 protein of influenza A virus is the enhancement of its IFN antagonist properties by stabilizing the NS1 dimeric structure...
  46. ncbi request reprint RNase L mediates transient control of the interferon response through modulation of the double-stranded RNA-dependent protein kinase PKR
    Khalid S A Khabar
    Department of Biological and Medical Research, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
    J Biol Chem 278:20124-32. 2003
    ..These results suggest a role for RNase L in the transient control of the IFN response and possibly of other cytokine and stress responses...
  47. ncbi request reprint ISG20, a new interferon-induced RNase specific for single-stranded RNA, defines an alternative antiviral pathway against RNA genomic viruses
    Lucile Espert
    UMR CNRS 5094, EFS, 240 avenue Emile Jeanbrau, 34094 Montpellier Cedex 5, France
    J Biol Chem 278:16151-8. 2003
    ..We thus show that, besides RNase L, ISG20 has an antiviral activity, supporting the idea that it might represent a novel antiviral pathway in the mechanism of IFN action...
  48. pmc Distinctive roles for 2',5'-oligoadenylate synthetases and double-stranded RNA-dependent protein kinase R in the in vivo antiviral effect of an adenoviral vector expressing murine IFN-beta
    Khaldun Al-Khatib
    Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
    J Immunol 172:5638-47. 2004
    ....
  49. pmc Interferon-regulated pathways that control hepatitis B virus replication in transgenic mice
    Luca G Guidotti
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    J Virol 76:2617-21. 2002
    ..Finally, RNase L(-/-) transgenic mice were undistinguishable from controls under basal conditions and after poly(I-C) or IFN-gamma administration, suggesting that RNase L does not modulate HBV replication in this model...
  50. ncbi request reprint Endowing RNase H-inactive antisense with catalytic activity: 2-5A-morphants
    Longhu Zhou
    Department of Chemistry, Northern Arizona University, Box 5698, Flagstaff, Arizona 86011 5698, USA
    Bioconjug Chem 16:383-90. 2005
    ..RNase L assays demonstrated that this novel 2-5A-antisense chimera had significant biological activity, thereby providing another potential tool for RNA ablation...
  51. pmc RNA-dependent protein kinase is required for alpha-1 interferon transgene-induced resistance to genital herpes simplex virus type 2
    Daniel J J Carr
    Department of Ophthalmology, DMEI 415, The University of Oklahoma Health Sciences Center, 608 Stanton L Young Blvd, Oklahoma City, OK 73104, USA
    J Virol 79:9341-5. 2005
    ....
  52. ncbi request reprint Critical role for the oligoadenylate synthetase/RNase L pathway in response to IFN-beta during acute ocular herpes simplex virus type 1 infection
    Bobbie Ann Austin
    Department of Ophthalmology, University of Oklahoma Health Sciences Center, Biomedical Sciences Building, 608 Stanton L Young Boulevard, Oklahoma City, OK 73104, USA
    J Immunol 175:1100-6. 2005
    ....
  53. ncbi request reprint Interferon-alpha-induced expression of phospholipid scramblase 1 through STAT1 requires the sequential activation of protein kinase Cdelta and JNK
    Ke Wen Zhao
    Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis, Chinese Ministry of Education, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine formerly Shanghai Second Medical University, Shanghai 200025, China
    J Biol Chem 280:42707-14. 2005
    ..In conclusion, our results suggest that the induction of PLSCR1 transcription through STAT1 depends upon sequential activation of PKCdelta and JNK...
  54. pmc RNase L plays a role in the antiviral response to West Nile virus
    Svetlana V Scherbik
    Department of Biology, Georgia State University, P O Box 4010, Atlanta, Georgia 30302 4010, USA
    J Virol 80:2987-99. 2006
    ..The results suggest that RNase L activation is not a major component of the Oas1b-mediated flavivirus resistance phenotype...
  55. pmc Identification of a novel Gammaretrovirus in prostate tumors of patients homozygous for R462Q RNASEL variant
    Anatoly Urisman
    Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, United States of America
    PLoS Pathog 2:e25. 2006
    ..These findings also raise questions about the possible relationship between exogenous infection and cancer development in genetically susceptible individuals...
  56. pmc PKR and RNase L contribute to protection against lethal West Nile Virus infection by controlling early viral spread in the periphery and replication in neurons
    Melanie A Samuel
    Department of Molecular Microbiology, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110, USA
    J Virol 80:7009-19. 2006
    ..Our data suggest that PKR and RNase L contribute to IFN-mediated protection in a cell-restricted manner and control WNV infection in peripheral tissues and some neuronal subtypes...
  57. pmc The lack of RNA-dependent protein kinase enhances susceptibility of mice to genital herpes simplex virus type 2 infection
    Daniel J J Carr
    Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
    Immunology 118:520-6. 2006
    ..Collectively, activation of PKR, but not of OAS, contributes significantly to the local control and spread of HSV-2 following genital infection...
  58. ncbi request reprint RNase L activity does not contribute to host RNA degradation induced by herpes simplex virus infection
    Tracy J Smith
    Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Box 8096, 660 S Euclid Avenue, St Louis, MO 63110, USA
    J Gen Virol 84:925-8. 2003
    ..Furthermore, the data show that HSV-1 does not significantly induce RNase L activity in murine embryo fibroblasts...
  59. ncbi request reprint Delivery of 2-5A cargo into living cells using the Tat cell penetrating peptide: 2-5A-tat
    Longhu Zhou
    Department of Chemistry and Biochemistry, Northern Arizona University, Flagstaff, AZ 86011 5698, USA
    Bioorg Med Chem 14:7862-74. 2006
    ..This strategy provides a valuable vehicle for the entry of the charged 2-5A molecule into cells and may provide a means for targeted destruction of HIV RNA in vivo...
  60. pmc A phylogenetically conserved RNA structure in the poliovirus open reading frame inhibits the antiviral endoribonuclease RNase L
    Jian Qiu Han
    Department of Microbiology, School of Medicine, University of Colorado, Mail Stop 8333, Room P18 9116, 12800 E 19th Ave, Aurora, CO 80045, USA
    J Virol 81:5561-72. 2007
    ....
  61. pmc Alphavirus-based DNA vaccine breaks immunological tolerance by activating innate antiviral pathways
    Wolfgang W Leitner
    National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
    Nat Med 9:33-9. 2003
    ....
  62. ncbi request reprint Type I interferon inhibits antibody responses induced by a chimpanzee adenovirus vector
    Scott E Hensley
    Cell and Molecular Biology Group, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Mol Ther 15:393-403. 2007
    ..We conclude that type I IFN, when induced at high levels, can downregulate transgene product expression of Ad vectors and inhibit the formation of optimal antibody responses...
  63. ncbi request reprint Absence of PKR attenuates the anti-HSV-1 activity of an adenoviral vector expressing murine IFN-beta
    Khaldun Al-Khatib
    Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
    J Interferon Cytokine Res 22:861-71. 2002
    ....
  64. ncbi request reprint The murine double-stranded RNA-dependent protein kinase PKR and the murine 2',5'-oligoadenylate synthetase-dependent RNase L are required for IFN-beta-mediated resistance against herpes simplex virus type 1 in primary trigeminal ganglion culture
    Khaldun Al-Khatib
    Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
    Virology 313:126-35. 2003
    ....
  65. ncbi request reprint Synthesis, characterization, and biological properties of 8-azido- and 8-amino-substituted 2',5'-oligoadenylates
    Hiroaki Sawai
    Department of Applied Chemistry, Faculty of Engineering, Gunma University, Kiryu, Gunma 376 8515 Japan
    J Med Chem 46:4926-32. 2003
    ..In addition, these 8-azidoadenosine compounds may be considered as candidates for experimental therapeutic agents because they have enhanced stability to enzyme degradation while retaining the ability to activate RNase L...
  66. pmc Alphavirus minus-strand synthesis and persistence in mouse embryo fibroblasts derived from mice lacking RNase L and protein kinase R
    Dorothea L Sawicki
    Department of Microbiology and Immunology, Medical College of Ohio, Toledo, Ohio 43614, USA
    J Virol 77:1801-11. 2003
    ....
  67. ncbi request reprint Dichotomy between survival and lytic gene expression in RNase L- and PKR-deficient mice transduced with an adenoviral vector expressing murine IFN-beta following ocular HSV-1 infection
    Khaldun Al-Khatib
    Department of Ophthalmology, Microbiology, and Immunology, University of Oklahoma Health Sciences Center, HSC608 Stanton L Young Blvd, Oklahoma City, OK 73104, USA
    Exp Eye Res 80:167-73. 2005
    ..Collectively, the data suggest survival rates of viral-infected mice do not reflect the replication capacity as measured by herpes simplex virus type one lytic gene expression...
  68. pmc Involvement of the interferon-regulated antiviral proteins PKR and RNase L in reovirus-induced shutoff of cellular translation
    Jennifer A Smith
    Department of Microbiology, University of Minnesota, 420 Delaware St, Minneapolis, MN 55455, USA
    J Virol 79:2240-50. 2005
    ..In addition, our results suggest that reovirus has evolved effective mechanisms to avoid the actions of the interferon-stimulated antiviral pathways that include PKR and RNase L and may even benefit from their expression...
  69. ncbi request reprint Sensitivity of hepatitis C virus RNA to the antiviral enzyme ribonuclease L is determined by a subset of efficient cleavage sites
    Jian Qiu Han
    Department of Microbiology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    J Interferon Cytokine Res 24:664-76. 2004
    ..Our data indicate that a relatively small number of the UA and UU dinucleotides in HCV RNA mediate the overall sensitivity of HCV RNA to cleavage by RNase L...
  70. pmc Hepatitis C virus RNA: dinucleotide frequencies and cleavage by RNase L
    Christopher L Washenberger
    Department of Microbiology, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045, United States
    Virus Res 130:85-95. 2007
    ..Thus, RNase L can cleave HCV RNAs efficiently and variably reduced frequencies of UA and UU dinucleotides in HCV RNA ORFs are consistent with the selective pressure of RNase L...
  71. ncbi request reprint A convenient and sensitive fluorescence resonance energy transfer assay for RNase L and 2',5' oligoadenylates
    Chandar S Thakur
    Department of Chemistry, Cleveland State University, OH, USA
    Methods Mol Med 116:103-13. 2005
    ..The RNA probe used in the FRET assay was designed based on a region of respiratory syncytial genomic RNA. We demonstrate the utility of our FRET assay with several novel biostable analogs of 2-5A...
  72. pmc A viral RNA competitively inhibits the antiviral endoribonuclease domain of RNase L
    Hannah L Townsend
    Department of Microbiology, University of Colorado Denver, School of Medicine, Aurora, Colorado 80045, USA
    RNA 14:1026-36. 2008
    ..Consistent with the kinetic profile of a competitive inhibitor, the viral RNA inhibited the constitutively active endoribonuclease domain of RNase L. We call this viral RNA the RNase L competitive inhibitor RNA (RNase L ciRNA)...

Research Grants32

  1. Antiviral Mechanisms of 2-5A Dependent RNase L
    Robert H Silverman; Fiscal Year: 2010
    ..The knowledge to be gained may thus lead to strategies for controlling important human viral pathogens. Therefore, there are cogent and health-related justifications for these studies. ..
  2. Antiviral Mechanisms of 2-5A Dependent RNase L
    Robert Silverman; Fiscal Year: 2007
    ..The knowledge to be gained may thus lead to strategies for controlling important human viral pathogens. Therefore, there are cogent and health-related justifications for these studies. ..
  3. Role of RNase L in the Biology of Prostate Cancer
    Robert Silverman; Fiscal Year: 2006
    ..The experiments described in this PROPOSAL describe a previously unexplored area of research that may bring us closer to the eventual goal of understanding a molecular basis for prostate cancer. ..
  4. Antiviral Mechanisms of 2 5A Dependent RNase L
    Robert Silverman; Fiscal Year: 2004
    ..Therefore, continuation of this PROJECT is expected to lead to the eventual development of novel strategies for treatment of viral infections and cancer. ..
  5. Antiviral Mechanisms of 2 5A Dependent RNase L
    Robert Silverman; Fiscal Year: 2003
    ..Therefore, continuation of this PROJECT is expected to lead to the eventual development of novel strategies for treatment of viral infections and cancer. ..
  6. Role of Phospholipid Scramblase in Interferon Action
    Robert Silverman; Fiscal Year: 2002
    ..abstract_text> ..
  7. REGULATION OF 2-5A-DEPENDENT RNASE LEVELS OF INTERFERON
    Robert Silverman; Fiscal Year: 1993
    ..Because the 2-5A system has the ability to inhibit both virus replication and neoplastic cell growth this project directly impacts on the control of virus infection and cancer in man...
  8. ANTIVIRAL MECHANISMS OF 2 5A DEPENDENT RNASE
    Robert Silverman; Fiscal Year: 1999
    ..This project may lead to the discovery and development of novel therapeutic agents for viral infections, cancer and other diseases. ..
  9. REGULATION OF 2-5A-DEPENDENT RNASE LEVELS OF INTERFERON
    Robert Silverman; Fiscal Year: 1992
    ..Because the 2-5A system has the ability to inhibit both virus replication and neoplastic cell growth this project directly impacts on the control of virus infection and cancer in man...
  10. Role of Phospholipid Scramblase in Interferon Action
    Robert Silverman; Fiscal Year: 2004
    ..abstract_text> ..
  11. Antiviral Mechanisms of 2 5A Dependent RNase L
    Robert Silverman; Fiscal Year: 2002
    ..Therefore, continuation of this PROJECT is expected to lead to the eventual development of novel strategies for treatment of viral infections and cancer. ..
  12. Antiviral Mechanisms of 2 5A Dependent RNase L
    Robert Silverman; Fiscal Year: 2006
    ..Therefore, continuation of this PROJECT is expected to lead to the eventual development of novel strategies for treatment of viral infections and cancer. ..
  13. Role of RNase L in the Biology of Prostate Cancer
    Robert Silverman; Fiscal Year: 2007
    ..The experiments described in this PROPOSAL describe a previously unexplored area of research that may bring us closer to the eventual goal of understanding a molecular basis for prostate cancer. ..
  14. Antiviral Mechanisms of 2-5A Dependent RNase L
    Robert Silverman; Fiscal Year: 2006
    ..The knowledge to be gained may thus lead to strategies for controlling important human viral pathogens. Therefore, there are cogent and health-related justifications for these studies. ..
  15. Antiviral Mechanisms of 2-5A Dependent RNase L
    Robert Silverman; Fiscal Year: 2009
    ..The knowledge to be gained may thus lead to strategies for controlling important human viral pathogens. Therefore, there are cogent and health-related justifications for these studies. ..
  16. Role of Phospholipid Scramblase in Interferon Action
    Robert Silverman; Fiscal Year: 2005
    ..abstract_text> ..
  17. Role of RNase L in the Biology of Prostate Cancer
    Robert Silverman; Fiscal Year: 2005
    ..The experiments described in this PROPOSAL describe a previously unexplored area of research that may bring us closer to the eventual goal of understanding a molecular basis for prostate cancer. ..
  18. Antiviral Mechanisms of 2 5A Dependent RNase L
    Robert Silverman; Fiscal Year: 2005
    ..Therefore, continuation of this PROJECT is expected to lead to the eventual development of novel strategies for treatment of viral infections and cancer. ..
  19. Role of RNase L in the Biology of Prostate Cancer
    Robert Silverman; Fiscal Year: 2004
    ..The experiments described in this PROPOSAL describe a previously unexplored area of research that may bring us closer to the eventual goal of understanding a molecular basis for prostate cancer. ..
  20. Role of Phospholipid Scramblase in Interferon Action
    Robert Silverman; Fiscal Year: 2001
    ..abstract_text> ..
  21. ANTIVIRAL MECHANISMS OF 2 5A DEPENDENT RNASE
    Robert Silverman; Fiscal Year: 2001
    ..This project may lead to the discovery and development of novel therapeutic agents for viral infections, cancer and other diseases. ..
  22. ANTIVIRAL MECHANISMS OF 2 5A DEPENDENT RNASE
    Robert Silverman; Fiscal Year: 2000
    ..This project may lead to the discovery and development of novel therapeutic agents for viral infections, cancer and other diseases. ..
  23. Role of Phospholipid Scramblase in Interferon Action
    Robert Silverman; Fiscal Year: 2003
    ..abstract_text> ..